This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To fully utilize and apply our knowledge of CART peptides, identification and cloning of the CART receptor is essential (it is possible that there are several receptors). Screening for medications related to CART peptides requires an ability to work with and express the receptor. While there have been several publications on the receptor, we have begun an intensive study with the goal of improving assays and a cloning of the receptor. The CART receptor binding assay has been standardized, and levels of specific binding in several cell lines have been measured. Also, by using a relatively rare technical approach, we have been able to identify specific CART receptor binding in rat brain for the first time. Another approach to finding the CART peptide receptor has been to study known orphan receptors (an orphan is a receptor that is known, but whose activating substrate is unknown). Knockout mice with deletions of specific orphan receptors are being tested for responses to CART peptides. We continue to make significant progress identifying the CART peptide receptor(s).